Protective effects and possible mechanisms of Centella asiatica (L.) urban extract against acute and chronic liver injury: Evidence from in vivo and in vitro studies

Protective effects and possible mechanisms of Centella asiatica (L.) urban extract against acute and chronic liver injury: Evidence from in vivo and in vitro studies
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积雪草城市提取物对急性和慢性肝损伤的保护作用和可能机制:来自体内和体外研究的证据

DOI:
10.1002/ptr.7024
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发表时间:
2021-01-18
影响因子:
7.2
通讯作者:
Yang, Xiaochun
Yang, Xiaochun
中科院分区:
医学2区
文献类型:
--
作者:
Lu, Jiabin;Chen, Chao;Yang, Xiaochun

文献摘要

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药物性肝损伤(DILI)已成为世界范围内一个重要的卫生保健问题。积雪草[专业]植Urban传统上用于预防或治疗各种疾病,但它是否对肝损伤有效仍不清楚。在这项研究中,多个实验模型,不同的损害程度和类型的肝损伤已建立,以评估的正丁醇提取物的积雪草(CA-BU)的保肝作用。我们的研究结果表明,CA-BU提高肝细胞L02细胞从过氧化氢诱导的氧化损伤的存活率以浓度依赖性的方式。我们进一步验证了CA-BU在对乙酰氨基酚诱导的急性肝损伤(临床上最常见的DILI之一)和CCl 4诱导的急性化学性肝损伤小鼠模型以及慢性酒精性脂肪性肝炎大鼠模型中的保肝作用。此外,我们还采用网络药理学方法来探索其潜在机制,并预测AKT 1、EGFR、VEGFA和STAT 3为潜在的治疗靶点。在后续的研究中,我们将着重于靶点的验证,并对CA-BU抗肝损伤的机制提供更深入的了解。最后,我们希望这些发现能为临床治疗急慢性肝损伤提供新的思路和见解。
Drug-induced liver injury (DILI) has become a significant health care problem worldwide. Centella asiatica (L.) urban was traditionally used to prevent or treat various diseases, yet whether it works on hepatic injury remains unclear. In this study, multiple experimental models with different damage degrees and types of liver injury have been established to evaluate the hepatoprotective effects of an n-butanol extract of Centella asiatica (CA-BU). Our results revealed that CA-BU improved hepatocyte L02 cells survival from H2O2-induced oxidative damage in a concentration-dependent manner. We further verified the hepatoprotective effects of CA-BU in mice models of acetaminophen-induced acute liver injury (one of the most common DILIs clinically) and CCl4-induced acute chemical liver injury, and a rat model of chronic alcoholic steatohepatitis. Furthermore, network pharmacology approaches were performed to explore the underlying mechanisms, and we predicted AKT1, EGFR, VEGFA, and STAT3 as the potential therapeutic targets. In follow-up studies, we will focus on targets verification and provide a deeper insight into the mechanisms of CA-BU against liver damage. Finally, we hope that these findings will provide new ideas and insights for the treatment of acute or chronic liver injury in the clinic.